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Biomedical subjects

R M Ferguson

Publications and source records attributed to R M Ferguson.

At least 19 recordsLinked to original sources

Importance of endothelial VCAM-1 for inflammatory leukocytic infiltration in vivo.

The microvascular endothelia of rejecting DBA/2----C57B1/6 murine cardiac allografts develop reactivity with the mAb M/K-2, which recognizes the murine homologue of the human leukocyte adhesion molecule VCAM-1. This reactivity does not develop in DBA/2----DBA/2 cardiac isografts or normal DBA/2 cardiac tissues. To determine whether endothelial VCAM-1 plays a role in allograft inflammation, cardiac allograft recipients were treated with M/K-2 antibody and monitored for leukocytic graft infiltration and graft survival. Treatment of the graft recipients with 200 micrograms/day M/K-2 Ig prolonged graft survival by 5 to 6 days (statistically significant); whereas treatment with 100 micrograms M/K-2 Ig every other day after transplant did not influence graft survival. Neither treatment interfered with leukocytic infiltration, as detected histologically or by limiting dilution analysis. The high dose treatment, but not the low dose treatment, resulted in high circulating levels of M/K-2, as detected by serum ELISA, and prominent antibody deposition on the graft vascular endothelia, as demonstrated by immunohistologic analysis. These data demonstrate that VCAM-1 is uniquely expressed on the vascular endothelia of rejecting murine cardiac allografts, and that a mAb to VCAM-1 can interfere with the allograft rejection process. Although this antibody can interfere with lymphocyte-endothelial adhesion in vitro, it has little effect on leukocytic infiltration in rejecting allografts suggesting that this process does not depend exclusively on VCAM-1 expression.

Animals

Minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in type 1 (insulin-dependent) diabetic pancreas allograft recipients.

Decreased insulin sensitivity and glucose-dependent glucose disposal (glucose effectiveness) have been demonstrated in poorly-controlled Type 1 (insulin-dependent) diabetic patients. We have therefore examined the effects of successful pancreas transplantation that results in long-term physiologic normoglycaemia as measured by insulin sensitivity index and glucose effectiveness in 14 Type 1 diabetic recipients (Group 1) using the Bergman minimal model method. Their results were compared with those of five non-diabetic patients with kidney transplant alone (Group 2) and 10 healthy control subjects (Group 3). Mean plasma glucose levels were indistinguishable in Group 1 when compared to Groups 2 and 3. However, mean basal plasma insulin levels were two- and eight-fold greater in Group 1 (36 +/- 6 microU/ml) than in Group 2 (17 +/- 7 microU/ml) and Group 3 (4.5 +/- 0.6 microU/ml), respectively. Following intravenous glucose (t = 0 min) and tolbutamide (t = 20), peak incremental insulin levels were significantly (p less than 0.001) greater in Group 1 vs Groups 2 and 3. Mean insulin sensitivity index was 65% and 50% lower in Group 1 (2.89 +/- 0.45) and Group 2 (4.11 +/- 1.30), respectively, when compared to Group 3 (8.40 +/- 1.24 x 10(-1) min-1 (microU/ml)-1. In contrast, glucose effectiveness was similar in the three groups (Group 1, 2.48 +/- 0.26; Group 2, 2.05 +/- 0.21; and Group 3, 2.10 +/- 0.17 x 10(-2).min-1). We conclude that, despite prednisone-induced insulin resistance, normal glucose tolerance is achieved by hyperinsulinaemia and normalisation of glucose-dependent glucose disposal following pancreas-kidney transplantation in Type 1 diabetic patients.

Adult

Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients.

We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C-peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Combined kidney/pancreas transplantation at the Ohio State University Hospitals.

We conclude that combined kidney and pancreas transplantation is a safe and effective procedure to treat complicated Type I diabetic patients. It does carry significant potential for morbidity; therefore, it is essential that potential recipients understand these details prior to considering the procedure. Adequate preoperative screening for coronary artery disease is essential. The most difficult problem is dealing with early posttransplant dehydration and acidosis. More sensitive tools are needed to diagnose acute rejection in both combined kidney/pancreas recipients, as well as pancreas-alone grafts. Infectious complications are frequent, but most pose little morbidity. Currently, the incidence of early thrombosis is negligible. Even with these complications, overall excellent patient outcome demonstrates that kidney and pancreas transplantation should be the procedure of choice in well-selected Type 1 diabetics with end-stage renal disease.

Adult

Orthotopic liver transplantation with abdominal situs inversus and dextrocardia.

Anatomic anomalies may present technical difficulties during orthotopic liver transplantation. Abdominal situs inversus was considered a contraindication to liver transplantation. A successful liver transplant in a patient with both situs inversus and dextrocardia is described, along with a technical review.

Abnormalities, Multiple

Safety of simultaneous aortic reconstruction and renal transplantation.

Patients with aortic disease and end-stage renal failure who require both aortic reconstruction and renal transplantation (simultaneously or staged) pose a formidable clinical challenge. Traditionally, the performance of either one of these procedures has been viewed as a relative contraindication to the performance of the other. From 1978 to 1989, eight patients were referred to us with the combination of aortic disease and end-stage renal failure. Seven had aneurysmal disease and one had aorto-iliac occlusive disease. Five patients presented with their diseases sequentially and had two sequential operations, with a mean interval of 4 years between procedures. Three patients presented with their diseases simultaneously and underwent simultaneous aortic reconstruction and living related renal transplantation. All patients were followed up for a mean interval of 4.5 years. By life-table analysis, the 5-year renal graft survival was 100%, the primary aortic graft patency was 82%, and the secondary aortic graft patency was 100%. The only death in this series occurred 11 years after aortic reconstruction and 4 months after a renal transplantation and was due to overwhelming cytomegalovirus sepsis. There were no significant differences between the simultaneous and staged groups in terms of operative mortality, postoperative complications, transplant function, or aortic graft patency. From this experience, we conclude that: (1) patients who present simultaneously with aortic disease and end-stage renal failure can safely undergo simultaneous aortic reconstruction and renal transplantation; (2) patients who present with these two diseases sequentially can undergo a second reconstructive procedure with very low operative morbidity and mortality rates; (3) when these two procedures have been performed sequentially, the second procedure has not significantly altered the 30-day or 5-year results of the first procedure; and (4) the 30-day and 5-year results of each procedure have been excellent regardless of the temporal sequence in which they were performed.

Adult